The goal of this proposal to study the genetic variability of the human immunodeficiency virus type l (HIV-l), the causative agent of the acquired immunodeficiency syndrome (AIDS). Specifically, we are interested in the temporal relationship and sequence variability between the integrated proviral DNA and viral RNA during HIV-1 infection and the phenotypic consequences of genome variation of HIV-1 under selective pressure. Our specific aims are to examine: l) the temporal variations in proviral DNA in peripheral blood monocyte cells (PBMC) and viral RNA during active HIV-1 infection; 2) the evolution of proviral DNA and plasma viral RNA sequences during antiretroviral therapy to suppress HIV-1 replication; and 3) the replicative fitness of zidovudine and lamivudine-resistant mutant HIV-1 as compared to that of wild type HIV- 1. The proposed research will further our understanding of population dynamics of cells infected with HIV-1 as well as the genetic variability of HIV-1 and its phenotypic consequences, particularly during antiretroviral therapy, and may aid in designing effective antiretroviral therapy regimens to treat AIDS.